The present study was designed to investigate the effect of membrane proteoglycans (MPG) from Klebsiella pneumoniae on the function of human natural killer (NK) cells. MPG combined with bacterial ribosomes from Klebsiella pneumoniae, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae, constitute a bacterial immunomodulator (MS D 53), currently in clinical use. Human peripheral blood lymphocytes (PBL) exposed in vitro to MPG or MS D 53 for 20 h showed enhanced NK cytotoxicity. Augmentation of NK cytotoxicity depended upon a direct effect on NK cells, inasmuch as these compounds were also effective on highly purified large granular lymphocytes (LGL). We also studied the effects of MPG on non-cytotoxic functions of NK cells, namely in vitro locomotion and production of IL-1. MPG (and MS D 53) induced IL-1 release in LGL. Moreover, MPG-treated LGL showed enhanced locomotory activity, as assessed by measuring the penetration into nitrocellulose filters. The capacity of MPG (and MS D 53) to activate cytotoxic and noncytotoxic functions of NK cells may contribute to enhancement of nonspecific resistance in vivo after treatment with this agent.